Bifunctional Lewis-Acid-/Ammonium-Salt-Catalysis as a Tool for Asymmetric Cyanations: 1,2-Addition, 1,4-Addition and Nucleophilic Ring Opening Reactions

双功能路易斯酸/铵盐催化作为不对称氰化的工具：1,2-加成、1,4-加成和亲核开环反应

• 批准号: 404194277
• 负责人: Professor Dr. René Peters
• 金额: --
• 依托单位: Institut für Organische Chemie (IOC)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2018
• 资助国家: 德国
• 起止时间: 2017-12-31 至 2021-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/404194277?language=en
• 关键词: Bifunctional; Lewis; Acid; Ammonium; Salt

In 2008, our research group has introduced the strategy of the cooperation between a Lewis acid and an aprotic onium salt within a bifunctional chiral catalyst for enantioselective reactions. Whereas the Lewis acid activates the electrophile by lowering the LUMO energy, the aprotic onium function directs an anionic nucleophile by ion pair interactions towards the electrophile. This allows for control over the trajectory of the nucleophile and thus face selectivity of the attack. At the same time the almost naked character of the anionic nucleophile increases its reactivity compared to a metal bound nucleophile. These advantages of increased reactivity and improved stereocontrol were used by us in the last years for different reaction types - cycloadditions, 1,2-additions, desymmetrizations - thus establishing proof of principle for the new concept. In this context, we have recently described a remarkably robust chiral salen-Al-F-catalyst with appended ammonium salt side chain, which allowed for an activity increase by 1-2 orders of magnitude for asymmetric carboxycyanations of aldehydes compared to the best literature known cyanation catalysts. For this cooperative asymmetric Lewis acid/onium salt catalysis TONs of up to nearly 104 could be achieved in highly enantioselective reactions. The focus of the described program is the investigation of this dual activation strategy for the addition of cyanide to other electrophiles like imines or different Michael-acceptors to provide value-added chiral, functionalized nitrile building blocks with high efficiency. The latter are attractive for many subsequent synthetic transformations due to the versatility of cyano groups (e.g.: reduction to amines, hydrolysis to carboxylic acids). The major goal is to enter a new level of activity for the proposed reactions, similar as for the mentioned carboxycyanations, which was not possible so far with established catalyst concepts. By using KCN as the only and non-volatile, cost-efficient cyanide source (avoiding the use of expensive volatile TMSCN) practicality of these transformations should also be improved rendering these reactions interesting from a technical and economical point of view as well. By mechanistic studies (kinetics, spectroscopy, DFT-calculations) we aim to learn more about the effective mode of action for this kind of dual activation. On long term this should permit to rationally plan other transformations.

2008年，我们的研究小组介绍了双功能性手性催化剂中的刘易斯酸与抗蛋白盐之间合作的策略，以实现对映选择性反应。而路易斯酸通过降低Lumo能量来激活电力，而Aprototototot otototium函数通过离子对相互作用将阴离子亲核剂引导到电力机。这样可以控制核粒子的轨迹，从而面对攻击的选择性。同时，与金属结合的亲核试剂相比，阴离子亲核试剂的几乎赤裸特征增加了其反应性。在过去的几年中，我们使用了反应性提高和改善的立体控制的这些优势，用于不同的反应类型 - 环加成，1,2个添加，1,2个粘结，desimportizatization-因此建立了新概念的原理证明。在这种情况下，我们最近描述了具有添加的铵盐侧链的一种非常强大的手性促催化剂，与最佳文献已知的氰化催化剂相比，醛的不对称羧基化的活性增加了1-2个数量级。对于这种合作的不对称刘易斯酸/盐盐催化吨，可以在高度对映选择性反应中实现近104吨。所描述的程序的重点是对这种双重激活策略的研究，以将氰化物添加到其他电物质或不同的迈克尔 - 受体受体，以提供高效率的增值性手性，功能化的氮基块。由于氰基组的多功能性（例如：还原为胺，水解为羧酸），后者对许多随后的合成转化具有吸引力。主要目标是对提出的反应进行新的活动水平，类似于上述羧基糖化，这是迄今为止已建立的催化剂概念不可能的。通过将KCN用作唯一的非挥发性，具有成本效益的氰化物来源（避免使用昂贵的挥发性TMSCN）的实用性，也应改善从技术和经济的角度来提高这些反应。通过机械研究（动力学，光谱，DFT计算），我们旨在更多地了解这种双重激活的有效作用方式。从长远来看，这应该允许合理地计划其他转型。